This invention relates to a process for preparing the active metabolite of an angiotensin II antagonist from its pro-drug compound. The active metabolite obtained can then be administered as an antihypertensive agent to a person in need of such treatment.
Administration of the active metabolite as opposed to its pro-drug analog is beneficial to a person receiving such treatment as the metabolite does not have to undergo any further, biochemical (i.e., metabolic) change by the body, but is available to be delivered by the body to its site of action. In addition, the active metabolite is about twenty times more potent than its pro-drug analog so that less metabolite is needed to achieve the same therapeutic effect as its pro-drug.
Administration of the pro-drug analog, on the other hand, requires the body to biochemically transform (i.e., metabolize) the pro-drug analog to its active, metabolic form. Usually, this biochemical transformation occurs in the renal system (generally, the kidney) causing the body to work harder and raising the possibility of creating adverse side effects.
The pro-drug analog compound used in the process of this invention is a substituted imidazole as disclosed in European Patent Application 253,310, published Jan. 20, 1988, which is included herein by reference. This European Application also discloses a two-step process for obtaining an active substituted imidazole metabolite from its pro-drug analog. This two-step process requires two oxidation reactions to obtain the desired, active metabolite. However, the metabolite obtained from this two-step process is difficult to purify and results in low yields of the desired metabolite.